The importance of fungal infection in gastroenterology is either overestimated, or vice versa, is not properly appreciated. Clear overdiagnosis often occurs. For example, based on the presence of Candida fungi in the culture of a smear from the oral mucosa in a person without signs of stomatitis, or in the analysis of feces “for dysbiosis” of a patient with irritable bowel syndrome, a diagnosis of candidiasis or even “systemic mycosis” is established. At the same time, it is completely ignored that the fungus is a human commensal and is widespread in the environment (such as Candida, Aspergillus). Therefore, the excretion of, say, Candida from the surface of the skin, mouth, sputum, urine and feces should be interpreted with caution.
It should always be borne in mind that many fungi do not exhibit pathogenic properties if the host is not weakened. Violations of the anatomical, physiological and immunological mechanisms of the body’s defense create conditions for the development of an infectious process caused by its own under normal conditions non-pathogenic microflora or saprophytic microorganisms from the environment.
The conditions for the development of opportunistic infections include: treatment with corticosteroids, immunosuppressants, antimetabolites, antibiotics; AIDS and other immunodeficiency conditions; serious metabolic disorders (eg, diabetes mellitus, kidney failure); neoplasms and anticancer therapy. Fungal lesions, including those of the gastrointestinal tract, developing against the background of a serious illness, must be recognized in time and adequately treated, since this infection can have a negative effect on the prognosis of the underlying disease. A correctly recognized fungal infection of the gastrointestinal tract often provides an underlying diagnosis. Thus, candidiasis of the oral cavity and esophagus is one of the “calling cards” of AIDS. One of the important gastroenterological aspects of the problem under consideration is also the fact that fungal infection can be a complication of enteral and especially parenteral nutrition.
Most often in patients with suppressed immunity, infection with Candida albicans is noted, less often with other representatives of the genus Sandida.
For candidal stomatitis, a white bloom is characteristic, slightly rising above the mucous membrane of the oral cavity and resembling curdled milk or cottage cheese. When plaque is removed, a hyperemic surface is exposed, which may bleed slightly (pseudomembranous form). With an atrophic form, the lesions look like erythema. Symptoms include dryness, burning, and frequent loss of taste. Candidal stomatitis is widespread among AIDS patients (one of the most frequent manifestations of the disease), as well as with the use of antibiotics, corticosteroids and anticancer agents.
Fungal esophagitis – most often candidal. They develop in immunodeficiency states, antibiotic therapy, often in patients with diabetes mellitus (a high concentration of glucose in saliva is favorable for the growth of fungi), in people of old age or with impaired trophological status. Fungal esophagitis also occurs with achalasia of the cardia, other movement disorders, for example, within the framework of scleroderma, and with esophageal stenosis. Clinically, fungal esophagitis is manifested by dysphagia and single phagia (painful swallowing). In severe cases, specific esophagitis can be complicated by bleeding, perforation, esophageal stricture, or the development of candidomycotic sepsis. Endoscopic examination reveals yellow-white relief overlays on the hyperemic mucous membrane of the esophagus. X-ray examination can reveal multiple filling defects of various sizes. The diagnosis is confirmed by microscopic examination of smears obtained with esophagoscopy.
Complaints of dysphagia and discomfort behind the breastbone in a patient with AIDS serve as the basis for a broad differential diagnosis, since damage to the esophagus in these patients can be caused by viruses (herpes simplex, cytomegalovirus), and the development of Kaposi’s sarcoma, and other reasons. However, the diagnosis of candidal esophagitis cannot be called difficult. The presence of fungal stomatitis in an HIV-infected patient with dysphagia is likely to indicate the correct etiology of esophagitis, and endoscopy with microbiological or histological examination unambiguously establishes the diagnosis in 95.5% of cases (I. McGowan, IVD Weller, 1998).
With suppression of the immune system and a general weakening of the body, the development of fungal gastritis is possible, the most common causative agent of which are representatives of the genus Candida, Histoplasma, Mucor.
Candidiasis affecting the small and large intestine as the cause of diarrhea is not as common as it might seem at first glance. Diarrhea is one of the most common symptoms of immunodeficiency states, and not only infectious agents cause it. However, the role of fungal infections (including Candida) as a cause of diarrhea is small. So, in AIDS, the causative agents of the infectious process in the small and large intestine, accompanied by diarrhea, are, first of all, protozoa – Cryptosporidium, Microsporidium (Enterocytozoon beineusi), Isospora belli, Giardia lamblia. Of the viruses associated with AIDS with the development of diarrheal syndrome, cytomegalovirus and herpes simplex virus should be named, and from bacteria – Salmonella, Shigella, Campylobacter spp.
It is important to pay attention to a well-differentiated nosological unit – pseudomembranous colitis. It is an acute inflammatory bowel disease associated with antibiotic therapy. Its clinical presentation ranges from short-term to severe diarrhea with fever, dehydration, and complications. Cases of this disease with uremia, after cytostatic therapy are described. During colonoscopy, fibrinoid overlays are found on the mucous membrane, because of which the disease got its name. Despite the superficial resemblance to candidiasis (the onset of the disease is provoked by antibiotics, white overlays are detected on the mucous membrane), pseudomembranous colitis has nothing to do with this fungal infection. The causative agent of antibiotic-associated colitis (synonymous with pseudomembranous colitis) has been identified. This is Clostridium difficile – a gram-positive anaerobic. Antibiotic therapy, suppressing its own microflora, creates conditions for the reproduction of C. difficile and the manifestation of its pathogenic properties. The diagnosis is established on the basis of the identification of the pathogen in the feces or by the detection of C. difficile toxin. This digression on pseudomebranous colitis once again emphasizes the need for an adequate assessment of the clinical picture, instrumental examination data and laboratory tests. The diagnosis of a fungal infection, including candidiasis, should be based on as much information as possible.
The most common fungal infections of the gastrointestinal tract – candidiasis of the oral cavity and esophagus – have rather characteristic signs. For a correct diagnosis, obtaining a culture of the pathogen must be confirmed by characteristic clinical symptoms, with the exception of another etiology, as well as histological signs of tissue invasion. In the case of systemic candidiasis, a culture of the fungus from blood, cerebrospinal fluid, or tissue, such as a liver biopsy, helps to clarify the clinical signs – septicemia, meningitis, or liver damage.
Cryptococcus and Histoplasma are of much lesser importance in gastroenterology. As a rule, involvement in the pathological process with these fungal infections of the gastrointestinal tract and liver occurs in patients with immunodeficiency with disseminated form of the disease. Histoplasma capsulatum with hematogenous spread from the lungs affects the liver and spleen with symptoms of hepato- and splenomegaly, and the defeat of the gastrointestinal tract is accompanied by ulceration (especially often in the oral cavity). With AIDS, Cryptococcus neoformans and Histoplasma spp. with disseminated cryptococcosis and histoplasmosis, the liver is affected by the type of granulomatous hepatitis. Clinically and biochemically, there is cholestasis syndrome. To establish an accurate diagnosis, a liver biopsy is necessary, in which fungal tissue invasion will be proven.
Modern antifungal agents represent a very impressive arsenal.
Fluconazole (water-soluble triazole) highly selectively inhibits fungal cytochrome P450, blocks the synthesis of sterols in fungal cells. Today there is a domestic fluconazole – Flucostat. It is almost completely absorbed in the gastrointestinal tract, allowing for rapid achievement of adequate serum concentrations. It is used for candidiasis and cryptococcosis. In AIDS, for the treatment of cryptococcosis after a preliminary course of amphotericin B (without fluorocytosine or in combination with it, which is preferable), fluconazole is prescribed at 200 mg per day.
Ketoconazole (an imidazole derivative) has a broad spectrum of antifungal activity, but unlike fluconazole, it can cause a temporary blockage of testosterone and cortisol synthesis.
Fluorocytosine is incorporated into the cells of the fungus, where it is converted into 5-fluorouracil and inhibits thymidylate synthetase. Usually the drug is used to treat candidiasis, cryptococcosis, chromomycosis.
Amphotericin B acts on the sterols of the fungal membrane, disrupts its barrier functions, which leads to the lysis of fungi. The indications for its appointment are systemic mycoses – candidiasis, aspergillosis, histoplasmosis and others.
Given the severity of the disease that may lead to opportunistic infections, antifungal therapy often requires a combination of drugs, repeated courses, or supportive care.